Androgen Metabolism and Reproductive Outcome

The aim of this study is to determine maternal androgen metabolism during pregnancy and the impact of androgen disorders on mothers and infants.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome; Healthy Pregnant Women

Detailed Description

Women with polycystic ovary syndrome (PCOS) have an impaired fertility and significant higher complication rates during infertility treatment, pregnancy and the perinatal period. Complications include the occurrence of multiple gestations, ovarian hyper stimulation syndrome, early pregnancy loss, gestational diabetes, pregnancy-induced hypertension, pre-eclampsia and need for caesarean section. Moreover, their infants are more frequently born preterm, have higher perinatal mortality rates and are more often admitted to a neonatal intensive care unit. The etiology of PCOS is not particularly mapped, but a genetic background can be assumed by analyzing PCOS families. In utero androgen excess has also been suspected to be an important risk factor. Animal studies have demonstrated that intrauterine hyperandrogenic environment affects the offspring by leading to biochemical and morphological features of PCOS. Sex differences in prenatal androgen levels have been observed and testosterone levels in umbilical cord blood and in amniotic fluid are higher in healthy male babies than in healthy female babies. There are just a few reporting on the relation between maternal androgen levels during pregnancy and the respective offspring. The aim of this clinical study is to determine maternal androgen metabolism and the impact of androgen disorders on mothers and infants.

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Polycystic ovary Syndrome (PCOS): According to ethnicity and the criteria used for diagnosis, polycystic ovary syndrome (PCOS) affects between 2-13% of women of reproductive age (Asunción et al., 2000; Azziz et al., 2009; ESHRE/ASRM, 2004; Wang and Alvero, 2013).

Description

Inclusion Criteria:

• pregnant women with and without PCOS

Exclusion Criteria:

• unable to consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pregnant women with PCOS and offspring; Exposures of interest: Polycystic ovary Syndrome (PCOS) according to Rotterdam
Pregnant women without PCOS and offspring; Exposures of interest: Pregnant women without polycystic ovary Syndrome (PCOS) according to Rotterdam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
correlation of testosterone between mother and offspring	day of birth (within average 24 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
correlation of sexual hormon binding globulin between mother and offspring	day of birth (within average 24 hours)
correlation of thyroid-stimulating hormone between mother and offspring	day of birth (within average 24 hours)
correlation of androstendione between mother and offspring	day of birth (within average 24 hours)
correlation of anti muellerian hormon between mother and offspring	day of birth (within average 24 hours)
correlation of progesterone between mother and offspring	day of birth (within average 24 hours)
correlation of dehydroepiandrosteron between mother and offspring	day of birth (within average 24 hours)
correlation of Vitamin D levels between mother and offspring	day of birth (within average 24 hours)
correlation of prolactin between mother and offspring	day of birth (within average 24 hours)
correlation of insulin between mother and offspring	day of birth (within average 24 hours)
correlation of human growth hormon between mother and offspring	day of birth (within average 24 hours)
correlation of c-peptide between mother and offspring	day of birth (within average 24 hours)
correlation of cortisol between mother and offspring	day of birth (within average 24 hours)
correlation of luteinizing hormon between mother and offspring	day of birth (within average 24 hours)
correlation of follicle stimulating hormone between mother and offspring	day of birth (within average 24 hours)
correlation of estrogen levels between mother and offspring	day of birth (within average 24 hours)
maternal testosterone	six weeks after birth
maternal sexual hormon binding globulin	six weeks after birth
maternal thyroid-stimulating hormone	six weeks after birth
maternal androstendione	six weeks after birth
maternal anti muellerian hormon	six weeks after birth
maternal progesterone	six weeks after birth
maternal dehydroepiandrosteron	six weeks after birth
maternal Vitamin D levels	six weeks after birth
maternal prolactin	six weeks after birth
maternal insulin	six weeks after birth
maternal human growth hormon	six weeks after birth
maternal c-peptide	six weeks after birth
maternal cortisol	six weeks after birth
maternal luteinizing hormon	six weeks after birth
maternal follicle stimulating hormone	six weeks after birth
maternal estrogen levels	six weeks after birth

Collaborators and Investigators

• Sponsor: Medical University of Graz

Publications and helpful links

General Publications

• Abbott DH, Barnett DK, Bruns CM, Dumesic DA. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update. 2005 Jul-Aug;11(4):357-74. doi: 10.1093/humupd/dmi013.
• Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007 Aug 25;370(9588):685-97. doi: 10.1016/S0140-6736(07)61345-2.
• Barry JA, Kay AR, Navaratnarajah R, Iqbal S, Bamfo JE, David AL, Hines M, Hardiman PJ. Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels. J Obstet Gynaecol. 2010;30(5):444-6. doi: 10.3109/01443615.2010.485254.
• Anderson H, Fogel N, Grebe SK, Singh RJ, Taylor RL, Dunaif A. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol Metab. 2010 May;95(5):2180-6. doi: 10.1210/jc.2009-2651. Epub 2010 Mar 12.
• van de Beek C, Thijssen JH, Cohen-Kettenis PT, van Goozen SH, Buitelaar JK. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure? Horm Behav. 2004 Dec;46(5):663-9. doi: 10.1016/j.yhbeh.2004.06.010.
• Hickey M, Sloboda DM, Atkinson HC, Doherty DA, Franks S, Norman RJ, Newnham JP, Hart R. The relationship between maternal and umbilical cord androgen levels and polycystic ovary syndrome in adolescence: a prospective cohort study. J Clin Endocrinol Metab. 2009 Oct;94(10):3714-20. doi: 10.1210/jc.2009-0544. Epub 2009 Jun 30.
• Goodarzi MO, Guo X, Yildiz BO, Stanczyk FZ, Azziz R. Correlation of adrenocorticotropin steroid levels between women with polycystic ovary syndrome and their sisters. Am J Obstet Gynecol. 2007 Apr;196(4):398.e1-5; discussion 398.e5-6. doi: 10.1016/j.ajog.2006.12.009.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: April 3, 2014
• First Submitted That Met QC Criteria: April 3, 2014
• First Posted (Estimate): April 8, 2014

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: androgens; hyperandrogenism; polycystic ovary Syndrome; cordblood
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome
• Other Study ID Numbers: 03